Effect of the cationic polypeptide polylysine on neutral amino acid transport in isolated brain microvessels

Summary The functionality of isolated brain microvessels — used as anin vitro model of the blood-brain barrier — can be influenced by interaction with cationic proteins. The various polylysines (M_r ranging from 0.9 to 180 kDa) tested affected the activity of both the Na⁺-dependent (A) and the Na⁺-independent (L) systems for neutral amino acid transport. Exposure to the 180 kDa polylysine caused a conspicuous inhibition of both transport systems, associated to an increased passive permeability. There was a constant, M_r-dependent, inhibition of the the L-system-mediated uptake of hydrophobic neutral amino acids. The activity of the A-system was enhanced, upon exposure to polymers larger than 22 kDa reaching its peak at 68 kDa and and declining at higher M_r values. The effect which was Na⁺-ions dependent and abolished by phloretine, could be essentially ascribed to an increased affinity of the MeAIB for its carrier (K_m value decreasing from 265 to 169µM in presence of 68 kDa polylysine).